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GeneBe

5-134661437-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_021982.3(SEC24A):c.416A>C(p.Gln139Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SEC24A
NM_021982.3 missense

Scores

7
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44
Variant links:
Genes affected
SEC24A (HGNC:10703): (SEC24 homolog A, COPII coat complex component) The protein encoded by this gene belongs to a family of proteins that are homologous to yeast Sec24. This protein is a component of coat protein II (COPII)-coated vesicles that mediate protein transport from the endoplasmic reticulum. COPII acts in the cytoplasm to promote the transport of secretory, plasma membrane, and vacuolar proteins from the endoplasmic reticulum to the golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEC24ANM_021982.3 linkuse as main transcriptc.416A>C p.Gln139Pro missense_variant 2/23 ENST00000398844.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEC24AENST00000398844.7 linkuse as main transcriptc.416A>C p.Gln139Pro missense_variant 2/232 NM_021982.3 P1O95486-1
SEC24AENST00000322887.8 linkuse as main transcriptc.416A>C p.Gln139Pro missense_variant 2/131 O95486-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 26, 2022The c.416A>C (p.Q139P) alteration is located in exon 2 (coding exon 2) of the SEC24A gene. This alteration results from a A to C substitution at nucleotide position 416, causing the glutamine (Q) at amino acid position 139 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.31
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.026
T;.
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.71
T;T
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.3
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-1.1
N;N
REVEL
Uncertain
0.54
Sift
Uncertain
0.0040
D;D
Sift4G
Benign
0.36
T;T
Polyphen
1.0
D;.
Vest4
0.75
MutPred
0.20
Gain of glycosylation at Q139 (P = 0.0444);Gain of glycosylation at Q139 (P = 0.0444);
MVP
0.95
MPC
0.56
ClinPred
0.86
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.25
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-133997127; API